A more objective staging of advanced prostate cancer—routine recognition of malignant endocrine structures: The assessment of serum TPS, PSA, and NSE values

Tarle, Marko; Kovačić, Ksenija; Frković‐Grazio, Snjez̆ana; Kraljić, Ivo

doi:10.1002/pros.2990240308

Cited by 34 publications

(31 citation statements)

References 19 publications

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“…However, their numbers increase in neoplastic growths, and their prevalence correlates with tumor size and progression to hormone-resistant states (4)(5)(6)(7)(8)(9), suggesting that they may play a role in advancing the disease. A large number of clinical studies have shown that prostatic neuroendocrine-like cells and their associated markers serve as prognostic indicators of poor patient survival (10)(11)(12)(13)(14)(15)(16), providing further support for a functional link between neuroendocrine-like cells and tumor progression.…”

Section: Introductionmentioning

confidence: 99%

Androgen-Independent Growth and Tumorigenesis of Prostate Cancer Cells Are Enhanced by the Presence of PKA-Differentiated Neuroendocrine Cells

et al. 2007

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The neuroendocrine status of prostatic adenocarcinomas is considered a prognostic indicator for development of aggressive, androgen-independent disease. Neuroendocrine-like cells are thought to function by providing growth and survival signals to surrounding tumor cells, particularly following androgen ablation therapy. To test this hypothesis directly, LNCaP cells were engineered to inducibly express a constitutively activated form of the cyclic AMP-dependent protein kinase A catalytic subunit (caPKA), which was previously found upon transient transfection to be sufficient for acquisition of neuroendocrine-like characteristics and loss of mitotic activity. Clonal cells that inducibly expressed caPKA enhanced the growth of prostate tumor cells in anchoragedependent and anchorage-independent in vitro assays as well as the growth of prostate tumor xenografts in vivo, with the greatest effects seen under conditions of androgen deprivation. These results suggest that neuroendocrine-like cells of prostatic tumors have the potential to enhance androgenindependent tumor growth in a paracrine manner, thereby contributing to progression of the disease. [Cancer Res 2007;67(8):3663-72]

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Section: Introductionmentioning

confidence: 99%

Androgen-Independent Growth and Tumorigenesis of Prostate Cancer Cells Are Enhanced by the Presence of PKA-Differentiated Neuroendocrine Cells

et al. 2007

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“…The presence of extensive multifocal NE features in tumors is an indication of increased aggressiveness and androgen independence (11)(12)(13). While the prognostic value of tumor NE status remains controversial, a strong link between NE status and long term, disease-specific survival has been reported (14).…”

mentioning

confidence: 99%

Activated 3′,5′-Cyclic AMP-dependent Protein Kinase Is Sufficient to Induce Neuroendocrine-like Differentiation of the LNCaP Prostate Tumor Cell Line

Cox¹,

Deeble²,

Bissonette³

et al. 2000

Journal of Biological Chemistry

112

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Neuroendocrine (NE) differentiation within prostate tumors is proposed to be a contributing factor in disease progression. However, the cellular origin and molecular mechanism controlling differentiation of prostatic NE cells are unresolved. The prostate tumor cell line, LNCaP, can reversibly acquire many NE characteristics in response to treatment with ␤-adrenergic receptor agonists and activators of adenylate cyclase. In this study, we demonstrate that these treatments induce protein kinase A (PKA) activation in LNCaP cells and that ectopic expression of a constitutively activated form of the PKA catalytic subunit, CI␣, results in acquisition of NE characteristics, including the extension of neuritic processes, cessation of mitotic activity, and production of neuron-specific enolase. Forskolin-, epinephrine-, and isoproterenol-dependent NE differentiation of LNCaP cells was significantly inhibited by expressing a dominant negative mutant of the PKA regulatory subunit, RI␣. These results demonstrate that prostatic NE differentiation in response to these agents depends on PKA activation, and this signaling pathway may provide a therapeutic target for treating advanced forms of prostate cancer.Efforts to develop novel therapeutic strategies for treating advanced prostate cancer have resulted in a considerable interest in the potential role of prostatic neuroendocrine (NE) 1 cells in disease progression (reviewed in Refs. 1 and 2). It has become evident that NE cells are a normal component of both the developing and mature prostatic epithelium and are postulated to be derived from stem cells common to both the exocrine and basal cell populations (3, 4). NE cells produce a variety of neurosecretory products that exhibit growth-promoting activities, including parathyroid hormone-related peptides, neurotensin, serotonin, calcitonin, and bombesin-related peptides (5-9), suggesting that these cells function through endocrine/paracrine mechanisms to regulate the normal development and secretory activity of the prostate.Virtually all prostatic adenocarcinomas contain foci of cells with NE characteristics (10). The presence of extensive multifocal NE features in tumors is an indication of increased aggressiveness and androgen independence (11-13). While the prognostic value of tumor NE status remains controversial, a strong link between NE status and long term, disease-specific survival has been reported (14). Tumor cell populations become enriched for NE cells following long term anti-androgen therapy (15), and although the NE cells appear to be nonmitotic, the carcinoma cells adjacent to these NE foci have been noted to exhibit increased proliferative activity (16, 17). These studies suggest that NE cells that develop within prostate tumors may produce neurosecretory factors that contribute to increased malignancy and decreased responsiveness to androgen ablation therapy.The androgen-responsive prostate tumor cell line, LNCaP, has emerged as a useful model for testing the development of a NE phenotype in adenocarcinoma ...

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“…E . U | |W | f f i X | and hepatic or renal impairment (Tarle et al, 1994), the patients Si S3 S5 S7 Cl C3 C5 C7 were divided into two groups: one group (n = 8) with apparent non-50-T specific TPS increases during successful androgen ablation therapy 20 (TPS > 80 U ml-' in the S6-S8 observation period, testosterone T,' > T T T < 1 nmol 1-1 and PSA < 2 ng ml-'); and a larger group (n = 15)…”

Section: Resultsmentioning

confidence: 99%

Measurements of tissue polypeptide-specific antigen and prostate-specific antigen in prostate cancer patients under intermittent androgen suppression therapy

Theyer

Holub²,

Dürer³

et al. 1997

Br J Cancer

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Summary The present study evaluated serial serum measurements of tissue polypeptide-specific antigen (TPS) in comparison with prostatespecific antigen (PSA) for assessment of tumour progression in patients with advanced prostate cancer receiving intermittent androgen suppression therapy (IAS). Twenty-three men were recruited into an IAS trial consisting of an initial 8 months of androgen suppression, followed by cycles of treatment cessation and resumption of therapy upon increases of PSA > 20 ng ml-' to prolong the hormone responsiveness of the tumour cells. Periods of androgen suppression resulted in reversible reduction in serum testosterone (< 1.8 nmol l-1) and PSA (< 4 ng ml-') and decreases in tumour volume (mean reduction for first cycle 24 ± 10%), indicating partial growth arrest and apoptotic regression of the tumours. In contrast to PSA values, non-specifically elevated TPS values were found in 8 of 23 patients. In 15 of 23 patients, TPS fell during periods of apoptotic tumour regression and increased simultaneously with testosterone and preceded the increases in PSA by 2 months during the period of treatment cessation. Although TPS represents a highly sensitive marker of tumour proliferation in this IAS clinical model of controlled tumour regression and regrowth, its low specificity compared with PSA limits its usefulness to monitoring of prostate cancer patients with proven absence of non-specific elevations of this marker.

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A more objective staging of advanced prostate cancer—routine recognition of malignant endocrine structures: The assessment of serum TPS, PSA, and NSE values

Cited by 34 publications

References 19 publications

Androgen-Independent Growth and Tumorigenesis of Prostate Cancer Cells Are Enhanced by the Presence of PKA-Differentiated Neuroendocrine Cells

Androgen-Independent Growth and Tumorigenesis of Prostate Cancer Cells Are Enhanced by the Presence of PKA-Differentiated Neuroendocrine Cells

Activated 3′,5′-Cyclic AMP-dependent Protein Kinase Is Sufficient to Induce Neuroendocrine-like Differentiation of the LNCaP Prostate Tumor Cell Line

Measurements of tissue polypeptide-specific antigen and prostate-specific antigen in prostate cancer patients under intermittent androgen suppression therapy

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